This proposal seeks to create a unique biomolecular dataset for the hematopoiesis research community by defining the molecular basis for functional heterogeneity among hematopoietic stem and progenitor cells (HSPC) in vivo in the mouse. This will be accomplished at a clonal level, sequentially using an engineered mouse strain that permits clonal tracking, cell isolation and molecular analyses. The bone marrow microenvironment will be analyzed under similar conditions of regions in physical proximity to hematopoietic stem and progenitor cells. Combined this dataset will provide a comprehensive molecular characterization of highly annotated in vivo cell behaviors under unperturbed and stress conditions. It involves three investigators with distinctive and complementary areas of expertise in the field of hematopoiesis, biomolecular computation and high resolution in vivo imaging. It involves distinctive tools generated by the interaction between these investigators and these disciplines. Successful accomplishment of this proposal will result in a unique resource coupling molecular data with functional attributes of individual clones of blood forming cells. It will be useful for the field and guide future studies by others to determine the molecula drivers of specific functions of stem and progenitor cells.